Noninvasive mechanical ventilation (NIV) is a universally recognized, effective method for type-2 respiratory failure (RF) treatment. Ventilator settings and treatment success rates vary, depending on machine configuration, provider experience, patient compliance, and, last but not least, the underlying condition and/or overlapping diseases. NIV is accepted by evidence-based medicine as a good treatment option for the following chronic diseases: amyotrophic lateral sclerosis (ALS), central hypoventilation syndromes (CHS), chronic obstructive pulmonary disease (COPD), kyphoscoliosis, obesity hypoventilation syndrome (OHS), Duchenne muscular dystrophy, and other muscular dystrophies and myopathies, as well as for patients with post-polio syndrome [1] and after spinal cord injuries (SCI) (usually level A of evidence). In acute respiratory failure (ARF), NIV is indicated in COPD exacerbations with pH < 7.35 (acute or acute-on-chronic respiratory failure), pneumonia in immunocompromised patients, cardiogenic pulmonary edema disqualified from interventional treatment, high-risk recurrent ARF after planned extubation or weaning from mechanical ventilation, ARF in declared “do not intubate” patients, and in acute respiratory deteriorations of patients on NIV due to chronic conditions (usually level A of evidence) [2].

Along with increasing knowledge and NIV development, the number of clinical indications proved by guidelines is constantly rising. On the other hand, international guidelines are usually disease specific; therefore, in clinical practice, it may be difficult to apply disease-specific ventilator settings and choose patients adequately. Recently, especially in aging Western populations, overlapping of frequent diseases, such as COPD, obstructive sleep apnea (OSA), OHS, and/or CHS secondary to cardiovascular complications, is often observed, but there is still insufficient high-level evidence on precise NIV applications and settings. Therefore, in overlapping diseases, the most important advice is watchful observation of the patient’s respiratory pattern, including rate and depth of use of additional respiratory muscles, as well as careful monitoring of measured variables such as minute ventilation, respiratory rate (RR), tidal volume (TV), and arterial blood gases in case of hospitalized patients. If possible, it is recommended to preset TV at 6-8 ml/kg (ideal body weight) in all adult patients, if different values are not indicated on the basis of pulmonary functional tests (spirometry and/or body plethysmography). As stated above, it is important to remember that overlapping is poorly addressed in the literature but may be frequently observed in real life, such as in the case of COPD and OSA/OHS overlapping, in which, if it is well tolerated by the patient and not previously determined by other anatomical and/or pathophysiological factors, pressure support (PS) should be primarily set on the basis of COPD guidelines, and expiratory positive airway pressure (EPAP) set on the basis of previous continuous positive airway pressure (CPAP) titration.